RU2014109395A - Ways to stimulate differentiation - Google Patents

Ways to stimulate differentiation Download PDF

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Publication number
RU2014109395A
RU2014109395A RU2014109395/10A RU2014109395A RU2014109395A RU 2014109395 A RU2014109395 A RU 2014109395A RU 2014109395/10 A RU2014109395/10 A RU 2014109395/10A RU 2014109395 A RU2014109395 A RU 2014109395A RU 2014109395 A RU2014109395 A RU 2014109395A
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RU
Russia
Prior art keywords
antagonist
candidate
id
usp1
cell
Prior art date
Application number
RU2014109395/10A
Other languages
Russian (ru)
Inventor
Вишва М. ДИКСИТ
Дороти М. ФРЕНЧ
Хизер Л. МАЕКЕР
Самуел А. УИЛЛЬЯМС
Original Assignee
Дженентек, Инк.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Priority to US201161535336P priority Critical
Priority to US61/535,336 priority
Application filed by Дженентек, Инк. filed Critical Дженентек, Инк.
Priority to PCT/US2012/055539 priority patent/WO2013040433A1/en
Publication of RU2014109395A publication Critical patent/RU2014109395A/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/502Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5073Stem cells
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90Enzymes; Proenzymes
    • G01N2333/914Hydrolases (3)
    • G01N2333/948Hydrolases (3) acting on peptide bonds (3.4)

Abstract

1. A method for screening and / or identifying a USP1 antagonist, a UAF1 antagonist and / or an ID antagonist that stimulates a change in a cell’s developmental pathway, said method comprising: comparing (i) an initial cell developmental pathway, wherein the initial cell developmental pathway is a developmental pathway an initial cell with (ii) a candidate cell development pathway, wherein the candidate cell development pathway is a pathway for the development of the original cell in the presence of a candidate antagonist of USP1, a candidate antagonist of UAF1 and / or a candidate antagonist and ID, wherein the candidate antagonist of USP1 binds USP1, wherein the candidate antagonist of UAF1 binds UAF1 and / or the candidate antagonist of ID binds ID, as a result of which the difference in the cell development path between the original path of development of the cell and the candidate path of cell development identifies the candidate antagonist of USP1 and / or candidate ID antagonist as a stimulating change in the cell development pathway. 2. The method of claim 1, wherein the USP1 candidate antagonist, UAF1 candidate antagonist and / or ID candidate antagonist is a USP1.3 candidate antagonist. The method of claim 1, wherein the candidate antagonist of USP1, the candidate antagonist of UAF1, and / or the candidate antagonist of ID is a candidate antagonist of ID.4. The method of claim 3, wherein the candidate ID antagonist is an ID1 candidate antagonist, an ID2 candidate antagonist, and / or an ID3.5 candidate antagonist. The method of claim 1, wherein the USP1 candidate antagonist, UAF1 antagonist and / or ID candidate antagonist is a UAF1.6 candidate antagonist. The method according to any one of paragraphs. 1-5, in which the initial path of cell development

Claims (25)

1. A method for screening and / or identifying a USP1 antagonist, a UAF1 antagonist and / or an ID antagonist that stimulates a change in a cell’s developmental pathway, said method comprising: comparing (i) an initial cell developmental pathway, wherein the initial cell developmental pathway is a developmental pathway an initial cell with (ii) a candidate cell development pathway, wherein the candidate cell development pathway is a pathway for the development of the original cell in the presence of a candidate antagonist of USP1, a candidate antagonist of UAF1 and / or a candidate antagonist and ID, wherein the candidate antagonist of USP1 binds USP1, wherein the candidate antagonist of UAF1 binds UAF1 and / or the candidate antagonist of ID binds ID, as a result of which the difference in the cell development path between the original path of development of the cell and the candidate path of cell development identifies the candidate antagonist of USP1 and / or Candidate antagonist ID as a stimulating change in cell development pathway.
2. The method according to claim 1, wherein the candidate antagonist of USP1, the candidate antagonist of UAF1 and / or the candidate antagonist of ID is a candidate antagonist of USP1.
3. The method of claim 1, wherein the USP1 candidate antagonist, UAF1 candidate antagonist and / or ID candidate antagonist is a candidate ID antagonist.
4. The method of claim 3, wherein the candidate ID antagonist is an ID1 candidate antagonist, an ID2 candidate antagonist, and / or an ID3 candidate antagonist.
5. The method of claim 1, wherein the USP1 candidate antagonist, UAF1 antagonist, and / or ID candidate antagonist is a UAF1 candidate antagonist.
6. The method according to any one of paragraphs. 1-5, in which the initial cell development pathway is a stem cell pathway.
7. The method according to claim 6, wherein the stem cell development pathway is a mesenchymal stem cell development pathway.
8. The method according to any one of paragraphs. 1-5, 7, in which the candidate cell development pathway is an osteoblast development pathway, a chondrocyte development pathway, or an adipocyte development pathway.
9. The method of claim 8, wherein the candidate cell development pathway is an osteoblast development pathway.
10. The method according to any one of paragraphs. 1-5, 7, 9, wherein the candidate USP1 antagonist, candidate UAF1 antagonist and / or candidate ID antagonist is an antibody that binds a polypeptide that binds a low molecular weight molecule or polynucleotide.
11. The method according to claim 1, wherein the USP1 antagonist, UAF1 antagonist and / or ID antagonist is a USP1 antagonist.
12. The method according to claim 1, wherein the USP1 antagonist, UAF1 antagonist and / or ID antagonist is an ID antagonist.
13. The method of claim 3, wherein the ID antagonist is an ID1 antagonist candidate, an ID2 antagonist candidate, and / or an ID3 antagonist.
14. The method according to claim 1, wherein the USP1 antagonist, UAF1 antagonist and / or ID antagonist is a UAF1 antagonist.
15. The method of claim 1, wherein the antibody is a human, humanized, or chimeric antibody.
16. The method of claim 1, wherein the antibody is an antibody fragment and the antibody fragment binds USP1, UAF and / or ID.
17. A method of stimulating a change in a cell’s developmental pathway comprising contacting the cell with an effective amount of a USP1 antagonist, a UAF1 antagonist and / or an ID antagonist.
18. The method of claim 17, wherein the cell is a cell with a stem cell development pathway (for example, by developing a mesenchymal stem cell).
19. A method of inducing cell cycle blockage, comprising contacting a cell with an effective amount of a USP1 antagonist, a UAF1 antagonist and / or an ID antagonist.
20. The method of claim 19, wherein the cell is a cell with a stem cell development pathway (for example, by developing a mesenchymal stem cell).
21. A method for treating a disease or disorder, comprising administering to an individual
an effective amount of a USP1 antagonist, a UAF1 antagonist and / or an ID antagonist.
22. The method according to p. 21, in which the individual is selected for treatment based on increased expression levels of one or more genes selected from the group consisting of CD90, CD105, CD106, USP1, UAF1 and ID (for example ID1, ID2 or ID3) ( for example, compared with an internal standard (e.g. CD 144)) or an individual is not selected for treatment based on low expression levels of one or more genes selected from the group consisting of CD90, CD 105, CD 106, USP1, UAF1 and ID (e.g. ID1 , ID2 or ID3) (e.g., compared to an internal standard (e.g. CD 144)).
23. The method according to any one of paragraphs. 21-22, in which the individual is selected for treatment based on low expression levels of one or more genes selected from the group consisting of p21, RUNX2, OSTERIX, SPARC / osteonectin, SPPl / osteopontin, BGLAP / osteocalcin and alkaline phosphatase (ALP) ( for example, compared to an internal standard (e.g. CD 144)) or an individual is not selected for treatment based on increased expression levels of one or more genes selected from the group consisting of p21, RUNX2, OSTERIX, SPARC / osteonectin, SPPl / osteopontin, BGLAP / osteocalcin and alkaline phosphatase (ALP) (e.g. measures compared to the internal standard (e.g. CD 144)).
24. The method according to any one of paragraphs. 21-22, in which the individual is likely to be sensitive to treatment based on increased expression levels of one or more genes selected from the group consisting of p21, RUNX2, OSTERIX, SPARC / osteonectin, SPPl / osteopontin, BGLAP / osteocalcin and alkaline phosphatase (ALP) (for example, compared to an internal standard (for example, CD 144)) (for example, from the point in time at the beginning, during or before the start of treatment to a later point in time) or the individual is probably not sensitive to treatment based on reduced levels of sludge expression the absence of a significant change in the expression levels of one or more genes selected from the group consisting of p21, RUNX2, OSTERIX, SPARC / osteonectin, SPPl / osteopontin, BGLAP / osteocalcin and alkaline phosphatase (ALP) (for example, compared with the internal standard (e.g. CD 144 )) (for example, from the point in time at the beginning, during or before the start of treatment to a later point in time).
25. The method according to any one of paragraphs. 21-22, wherein the USP1 antagonist, UAF1 antagonist and / or ID antagonist induces cell cycle blockage.
RU2014109395/10A 2011-09-15 2012-09-14 Ways to stimulate differentiation RU2014109395A (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US201161535336P true 2011-09-15 2011-09-15
US61/535,336 2011-09-15
PCT/US2012/055539 WO2013040433A1 (en) 2011-09-15 2012-09-14 Methods of promoting differentiation

Publications (1)

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RU2014109395A true RU2014109395A (en) 2015-10-20

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US (1) US20140199327A1 (en)
EP (1) EP2756300A1 (en)
JP (1) JP2014533927A (en)
KR (1) KR20140068062A (en)
CN (1) CN103930781A (en)
BR (1) BR112014005720A2 (en)
CA (1) CA2846083A1 (en)
MX (1) MX2014003094A (en)
RU (1) RU2014109395A (en)
WO (1) WO2013040433A1 (en)

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CA2846083A1 (en) 2013-03-21
MX2014003094A (en) 2014-04-25
WO2013040433A1 (en) 2013-03-21
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JP2014533927A (en) 2014-12-18

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